Inflammation is the foundation for cancer and degenerative/autoimmune diseases. Small changes in diet and exercise, e.g. omega-3 oils, vitamin D, low starch, and maintaining muscle mass, can dramatically alter predisposition to disease and aging, and minimize the negative impact of genetic risks. Based on my experience in biological research, I am trying to explain how the anti-inflammatory diet and lifestyle combat disease. 190 more articles at http://coolinginflammation.blogspot.com

Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:

Thursday, January 28, 2010

Scatological jokes are common. The guide on my Swedish language tour of Moscow in 1976, told a joke about Russians. She described Russian toilets that are dry, with a shelf for stools to drop upon and a lower hole in the back into which the stool is swept with water. This was contrasted to Western toilets that partially concealed the stools as they dropped into water. The joke was that Russians had no art, because they could easily observe their creations each morning.

You Are What You Eat and the Proof Is in the Toilet

Refer to Mr. Monastyrsky for a broad discussion of constipation and stool characteristics. This web site has lots of information about stool types, how to get them and how to change them. His recommendations to avoid constipation center on a healthy diet, like my Anti-Inflammation Diet, plus glutamine to help the gut heal.

Another useful perspective on gut flora is provided by a Nature web site on gut flora genomics. This site describes genomic research to show that changing diet changes relative proportions, but not the types of bacteria in gut flora. Each person has a recognizable, individual composition of gut bacteria.

Feces Is Primarily Bacteria

What you eat and your eating/health history determines your gut flora, and feces is made up of gut flora and some undigested food. Healthy bowel movement stools are made up of more than 50% bacteria and the consistency of the stools is determined by the bacterial content. Less bacteria means drier, harder stools. Bacteria hydrate stools and prevent constipation.

Pathogenic Gut Flora

Why does a total bowel irrigation with PEG, polyethylene glycol, make people with chronic diseases feel as good as if they had an antibiotic treatment (barring die off)? I think that the answer is that both disrupt and change the gut flora and in many cases disease symptoms are supported by an unhealthy gut flora/biofilms. In many cases, the antibiotic cannot have a lasting impact, because it is hard to kill bacteria in biofilms. PEG may actually clean out more of the biofilms, because it should also disrupt the polysaccharide matrix of the biofilms.

Disruption of Gut Flora Leads to Disease

Babies fed breastmilk vs. formula display very large difference in inflammation and susceptibility to disease. Formula causes gut inflammation and susceptibility to intestinal and respiratory diesease. Formula also causes a dramatic shift in gut flora from a simple flora dominated by Bifidobacter to a complex adult gut flora.

Gut Controls Immune System

The impact of the two different gut flora on development of the GI tract and on the newborn immune system is dramatic also. Remember that most of the immune system of the body is located in the lining of the gut and immune organs, such as the tonsils, are outgrowths of the GI tract. The thymus, which is responsible for producing T lymphocytes, is twice as large in breastfed babies. Thus, feedback from the gut of formula fed babies inhibits thymus and immune system development.

Change Your Gut Flora and Change Your Health

Experiments in mice, and I think in humans, have shown that changing the bacteria in the gut changes interactions with food. Exchanging gut bacteria between fat and lean individuals, causes fat people to lose weight and lean people to gain weight. I think that this indicates that gut flora participate in the so called metabolic set point, that determines if it is going to be easier to gain or lose weight. These experiments suggest that a powerful approach may be to eliminate the gut flora of individuals with chronic disease and replace it with healthy gut flora. This healthy gut flora, along with a healthy diet may make a powerful contribution to elimination of chronic diseases. Rosacea, which involves both the face and gut, might best be treated by topical antibiotics and anti-inflammatory agents, after the gut contribution has been eliminated by a fecal transplant with healthy gut flora/diet.

Anti-Inflammatory Diet Should Support Healthy Gut Flora

The efficacy of an anti-inflammatory diet (AID) should be displayed in reversal of inflammatory symptoms and unmemorable bowel movements. A gut and gut flora that resist inflammation as a result an AID, should also produce a healthier immune system and contribute to a reduction in chronic inflammation and disease. The gut may also have an impact on gut flora and a diet that does not contribute to inflammation in the body, e.g. lacks fructose and vegetable oils, may also support an anti-inflammatory gut flora.

Saturday, January 23, 2010

The Drs. Eades (Mary Dan and Michael) see eye to eye with me on the health benefits of a low carb diet for avoiding chronic inflammation, the foundation of most degenerative and autoimmune diseases and cancers. Recently they applied their clinical experience with the diets they developed to combat obesity to produce a book that focused on the protruding gut: The 6-Week Cure for the Middle-Aged Middle: The Simple Plan to Flatten Your Belly Fast! That book seemed to be a great way to introduce most people to a healthy diet based on obtaining calories from fat rather than carbs, so I featured it as the recommended book on my blog for the last several months. Two weeks ago my wife and I decided to practice what I preach and started The Cure.

The Cure Reduces Visceral Abdominal Fat

"The Cure” consists of three, 2-week blocks, that adapt the body metabolism to a new low carb, higher fat diet. The focus is to reduce visceral fat stored primarily in the abdomen. Equally important, from my perspective, are the changes that take place in the gut flora -- The Cure changes the composition of the gut flora to facilitate change in body fat and to restore complete function to the immune system.

Basic Outline of The Cure

The first two weeks of The Cure consist of three protein shakes (low carb flavored whey plus cream) and a very low carb meal each day. Weeks 3 and 4 are no-carb, dairy-free meals of meat/fish/eggs with calories from fat and protein only. The final two weeks are the new low carb, higher fat diet. Research on diet and gut flora would predict that the bacterial species in the gut stay basically the same and provide a recognizable individuality, but the relative quantity of each species in the gut changes to maintain body fat. The efficiency of the total gut flora would increase, if the diet resulted in weight loss and become less efficient, if there was increased fat deposition.

After the First Two Weeks of Protein Shakes

A diet of protein shakes changed my view of food. I was simply not hungry and cravings disappeared. My wife was shocked that she felt satisfied after drinking a shake and did not panic without snacks or seconds. It was relatively easy to eliminate most of the bad eating habits associated with weight gain. There was no problem about portion sizes or eating outside of meals. All of the bad habits became noticeable and I could see when I normally reached for some food out of boredom. There was simply no physiological support for snacking. Hydration is important and bowel movements were irregular as gut flora adapted to the severe change in diet. [Also note that the milk whey protein used in the shakes is high in lactoferrin, a protein found useful in controlling bacterial pathogens, e.g. Clostridium dificil, and intestinal candidiasis.]

Weight Loss Was Effortless

It was easy to drop some weight on the protein shakes. My wife (15 lbs) and I (5 lbs) both lost weight easily. This is significant, since neither of us was able to reduce our weights in the last several years. My weight at the start was 20 lbs over what I weighed as a high school gymnast. I didn’t feel like I had a lot of energy in the first two weeks of The Cure, so I slacked off on walking and weight training. Now that I am into the luxurious second phase with lots of meat, gaining strength by exercising is a pleasure.

Reduced Need for Fish Oil with Altered Gut Flora

Something that I need to highlight and that I attribute to the change in my gut flora, is a lowered need for fish oil. I was taking four fish oil capsules per day, to eliminate minor aches in my fingers. After the first two weeks of The Cure, without vitamin D supplements or fish oil, I still don’t have any finger aches. My wife, also no longer needs fish oil to make our 3-mile hikes along Indian Creek painless for her knees. The Cure seems to have uncovered a remaining source of inflammation in my previous diet. The most likely inflammatory candidate was the small amounts of grain and starch still in my old diet. It will be very easy for me to transition to a new anti-inflammatory diet more consistent with the one I have been advocating on this blog. I think that the anti-inflammatory diet would be a simple, healthy and enjoyable way to avoid most diseases or as an essential part in the treatment of most degenerative and autoimmune diseases and cancers.

My thanks go to the Drs. Eades for creating a smart diet sequence that alters gut flora for loss of visceral abdominal fat and provides a transition to a healthy low carb, increased fat diet. The diet sequence may also be useful in restoring gut flora destroyed by antibiotic use or dysbiosis indicated by constipation.

Wednesday, January 13, 2010

What does it take to make your face red? Excessive solar exposure can lead to apoptosis of skin cells overloaded with DNA damage and trigger inflammation: vasodilation, recruitment of neutrophils, swelling, etc. Similarly, a local infection can cause inflammation and the accumulation of neutrophils (see The Inner Life/Extravasation for slide show), lymphocytes, etc., that is observed as pus. These are general responses that occur in skin anywhere, but the face also blushes in response to emotional cues and flushes with exercise. Rosacea seems to involve all of these reactions to produce a variety of symptoms of wide severity. Here I try to provide an overview of the complex physiological interactions involved in rosacea.

Rosacea is Persistent Vasodilation of the Face with Accumulation of Neutrophils

The nervous and circulatory systems of the face are unique and provide numerous triggers for inflammation. Emotional blushing is a common trait among those who progress to rosacea, even though this type of vasodilation is not easily observed with some facial characteristics. Thus, many rosaceans claim to have never flushed before their first outbreak, but tests of skin circulation indicate that these individuals had skin types that prohibited display of the blushing. The face is also adapted to control brain temperature, so changes in body temperature, physical activity, etc. can also trigger flushing.

Facial Blood Circulation to Cool the Brain

The cooling of the blood as it traverses the facial skin is used to cool the brain during extensive exercise or in warm environments. This unique adaptation also means that control of facial vasodilation can potentially be disrupted in disease and cause symptoms of pathology. In rosacea, the brain cooling response is disturbed (see reference below), resulting in persistent vasodilation and suggesting that the unique control of inflammation in the face is why rosacea is limited to the face. The pattern of blood circulation in the face, however, only roughly approximates the inflammation pattern in rosacea.

Nerves to the Face
The face receives sensory branching from the trigeminal nerve. The enervation pattern of the branches matches emotional blushing, but they also appear to approximate the pattern of reddening in rosacea. It makes sense that rosacea involves nerve-triggered dilation of the blood vessels of the face. One contrast between emotional blushing and rosacea is that emotional blushing does not lead to the offloading of lymphocytes, whereas rosacea produces localization of neutrophils that exacerbate and prolong inflammation.

Cathelicidin, Vitamin D Receptor, DNA Complexes, Autoinflammation

A major component of the innate immune system is the group of basic antimicrobial peptides, cathelicidins. Cathelicidins are effective against bacteria and they are produced during inflammation and are partially controlled by the vitamin D receptor acting as a transcription factor. Thus, part of the action of vitamin D in providing protection against disease is by enhancing cathelicidin production. Cathelicidin action in the skin parallels the control of intestinal villi development by defensins, that are also basic antimicrobial peptides under the control of vitamin D. Cathelicidins also form complexes with host DNA from damaged cells. These cathelicin/DNA complexes bind to toll-like receptors (TLRs) and trigger inflammation. This reaction has been associated with psoriasis and may explain how neutrophil damage can perpetuate inflammation in rosacea.

Niacin Flushing Implicates Arrestins

The unique circulatory system of the face also makes it susceptible to flushing with niacin, a.k.a. nicotinic acid or vitamin B3. Niacin is cheaper and much more effective at raising HDL and lowering triglycerides and LDL than statins, but is not fully utilized because it also produces intense facial flushes. A recent article (below) has demonstrated that the lipid benefits can be separated from the flushing and implicated beta-arrestin 1 activation by niacin binding to GPR109A (G-protein-coupled receptor) as the triggering event. Arrestin, which is involved in clathrin-mediated endocytosis, activates phospholipase A2 that in turn releases arachidonic acid (ARA) from phospholipids. The ARA (that got into the phospholipids as the omega-6 fatty acid in vegetable oils) is converted by COX-2 into the inflammatory prostaglandin D2. This prostaglandin is what stimulates vasodilation. It is possible to produce chemicals that will stimulate the lipid metabolism alterations of niacin, without producing the arrestin activation and inflammation. Aspirin can be used to inhibit COX-2 and other parts of NFkB-mediated inflammation and eliminate the niacin flush. It is also interesting that the modified lipid metabolism of schizophrenics also eliminates niacin flushing. Salicylic acid, the same as the acetylsalicylic acid of Aspirin without the acetate, is also used in some topical applications to quiet the symptoms of rosacea. Arrestin activation may be involved in rosacea.

Gut Flora, Biofilms and Cryptic Bacteria

The gut is probably involved in most cases of rosacea and bacteria are also implicated by the modification of rosacea symptoms by antibiotics. This area has not been explored, but I suspect that gut flora controlled by diet, as well as pathogenic biofilms and cryptic bacteria, e.g. Clamydia pneumoneae, in facial tissue are involved in varying degrees in the panoply of pathologies called collectively, rosacea. Since the bacteria in contact with the gut determine the development of the lymphocytes in the lining of the gut, e.g. Tregs vs. T cells that fight infections, pathogenic gut biofilms may disrupt the normal function of the immune system and support rosacea. Die off and release of cell wall endotoxin from cryptic bacteria could explain the paradoxical inflammation in response to many treatments that are normally anti-inflammatory. I have discussed in another article potential approaches to strip off biofilms.

Treatment with Anti-Inflammatory Diet

The Anti-Inflammatory Diet (AID) and Lifestyle that I advocate on this blog would seem to be a natural cure for rosacea. It should eliminate the inflammatory background that supports rosacea and was probably essential for its development. This diet also eliminates acne, which is directly related to the accumulation of lymphocytes to make pus. Inflammation is also needed for the offloading of neutrophils that exacerbate inflammation in rosacea. Vitamin D is instrumental in cathelicidin production to eliminate cryptic bacteria.

In most cases of rosacea, the AID should be helpful. Eliminating dietary sources of inflammation, especially vegetable oils (the source of omega-6 fatty acids that are converted into inflammatory prostaglandins), should reduce rosacea symptoms.

In advanced, severe cases, however, it appears that maintenance of the suppression of the response to cryptic bacteria is required to prevent endotoxin-based inflammation. Thus, most treatments that decrease inflammation, e.g. omega-3 oils, vitamin D3, Vagal maneuvers, can paradoxically produce elevated inflammation. These treatments may also inadvertantly contribute to inflammation by upsetting pathogenic interactions between bacteria and intestinal cells. I have discussed these paradoxical ramifications in another article.

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About Me

I grew up in San Diego and did my PhD in Molecular, Cellular and Developmental Biology (U. Colo. Boulder). I subsequently held postdoctoral research positions at the Swedish Forest Products Research Laboratories, Stockholm, U. Missouri -Colombia and Kansas State U. I was an assistant professor in the Cell and Developmental Biology Department at Harvard University, and an associate professor and Director of the Genetic Engineering Program at Cedar Crest College in Allentown, PA. I joined the faculty at the College of Idaho in 1991 and in 1997-98 I spent a six-month sabbatical at the National University of Singapore. Most recently I have focused on the role of heparin in inflammation and disease.